Back to Search
Start Over
Beta- and alpha-adrenergic cross-signaling for L-type Ca current is impaired in transgenic mice with constitutive activation of epsilonPKC.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2004 Feb 13; Vol. 314 (3), pp. 749-54. - Publication Year :
- 2004
-
Abstract
- It is well established that beta-adrenoceptor stimulation activates PKA and alpha(1)-adrenoceptor stimulation activates PKC. In normal ventricular myocytes, acute activation of alpha(1)-adrenoceptors inhibits beta-adrenoceptor stimulated L-type Ca current (I(Ca-L)) and direct activation of epsilonPKC leads to I(Ca-L) inhibition. Because increased PKC activity has been observed chronically in in vivo setting such as failing human heart, we hypothesized that chronic in vivo activation of epsilonPKC alters I(Ca-L) and its response to adrenergic stimulation. Therefore, we investigated the interaction between beta- and alpha(1)-adrenoceptors vis-à-vis I(Ca-L) in myocytes from transgenic mice (TG) with cardiac specific constitutive activation of epsilonPKC (epsilonPKC agonist). Whole-cell I(Ca-L) was recorded from epsilonPKC agonist TG mice and age-matched non-TG (NTG) littermates under: (1) basal condition, (2) beta-adrenoceptor agonist, isoproterenol (ISO), and (3) ISO plus alpha(1)-adrenoceptor agonist, methoxamine. The present results are the first to demonstrate that chronic in vivo activation of epsilonPKC leads to reduced basal I(Ca-L) density. beta-adrenoceptor activation of I(Ca-L) is blunted in epsilonPKC agonist TG mice. alpha-adrenoceptor cross-talk with beta-adrenoceptor signaling pathways vis-à-vis L-type Ca channels is impaired in epsilonPKC agonist TG mice. The diminished response to ISO and methoxamine suggests a protective feedback regulatory mechanism in epsilonPKC agonist TG mice and could be vital in the settings of excessive release of catecholamines during heart failure.
- Subjects :
- Adrenergic alpha-1 Receptor Agonists
Animals
Electrophysiology
Enzyme Activation drug effects
Isoproterenol pharmacology
Methoxamine pharmacology
Mice
Mice, Transgenic
Myocytes, Cardiac drug effects
Myocytes, Cardiac physiology
Patch-Clamp Techniques
Protein Kinase C-epsilon
Signal Transduction
Calcium Channels, L-Type physiology
Protein Kinase C metabolism
Receptors, Adrenergic, alpha-1 metabolism
Receptors, Adrenergic, beta metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0006-291X
- Volume :
- 314
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 14741699
- Full Text :
- https://doi.org/10.1016/j.bbrc.2003.12.155